The long-term objectives of this research are: (1) to identify geometric features of the vasculature that enhance arterial susceptibility to atherosclerotic disease and can be used for early identification of individuals accordingly at risk, and (2) to understand the role of mechanical factors in the localization and pathobiology of atherosclerosis. To achieve the first objective, relationships are sought between in vivo measurements of the geometric features of human coronary arteries and the pathology of the vessels, with a focus on the early lesion. The second objective is furthered by computing the distribution of fluid dynamic and intramural stresses in selected vessel segments, and seeking correlations between these variables and the thicknesses of the vascular intima and media, as measured in vivo. Clinical biplane coronary cineangiograms of sixty patients at The Ohio State University and Wake Forest University School of Medicine will be processed digitally to reconstruct the three- dimensional (3-D) course of the medial axes of selected segments of the left anterior descending and right coronary artery trees. Quantitative geometric parameters of the segments, including both static and dynamic measures of arterial geometry and measures of vessel kinematics, will be obtained from the axes using objective computer algorithms. Variations in geometry among individuals will be assessed. Intravascular ultrasound (IVUS) records of the same segments will be obtained and processed to yield detailed measurements of vessel morphometry collocated to the vessel axes. Doppler flow data and phasic pressure will also be acquired. Relations will be sought between the geometric variables from the angiograms and morphometric parameters derived from the IVUS records; and analysis will take into account individual variability with respect to the traditional risk factors for atherosclerosis. The dynamic data from the angiograms will be used in model calculations to estimate the effect of vessel motion and bending on the flow fieled and wall stresses. For twelve cases, the angiographic and IVUS records will be used to describe the 3-D lumen and wall of a portion of the vessel in diastole. The flow fieled and wall stresses in this region will be simulated numerically, using the Doppler and pressure data as input; the first flow calculation will be validated experimentally. By comparing the computed distribution of stresses acting on and in the vessel segment against that of intima/media thickness, inferences will be drawn regarding the role of mechanical forces in relation to human atherosclerosis.